The Liverpool View: The unexpected victims of HIV/AIDS

Professor William A Paxton is a Prinicpal Investigator into Clinical Infection, Microbiology and Immunology at the University of Liverpool’s Institute of Infection and Global Health

“All scientists have that moment when an idea is initiated or when things come together and a project flourishes. One such moment for me came at a Keystone meeting in South Carolina in 1994.

It was here that I first met Gregg Consalves, an AIDS activist with Treatment Action Group (TAG) based in New York. I explained I wanted to set up a study of individuals who had been heavily exposed to HIV for many years but who had not been infected. Gregg got involved and within a week I had my first recruit: Steve Crohn who became the focal point of our research over the following years.

Resistant to infection

From studying Steve we identified that he had CD4 cells resistant to HIV infection and he carried a genetic alteration that was responsible. CD4 cells are the lymphocytes of the immune system that HIV usually infects and destroys. Steve helped identify a key molecule called CCRS that the virus requires to enter lymphocytes. Sadly Steve passed away on 24^th August this year when he committed suicide at 66 years of age (The Lancet; 382:1480).

Steve himself has described his own exposure to the AIDS epidemic in war terminology. I certainly would not like to conclude that Steve’s death stemmed from post-traumatic stress disorder or what’s otherwise known as ’survivor’s guilt’, but it certainly shouldn’t be ignored within the HIV/AIDS community.

Steve always was heartened to have contributed to the ’fight’ and in helping provide a pivotal piece of the jigsaw that saw Maraviroc, a CCR5 blocking antiretroviral drug, being brought quickly to the market.

There are other incidences where AIDS has unexpectedly taken its toll. One of the prominent activists in the early days in New York was Spencer Cox, who devised the first trial protocols for the testing of protease inhibitors, which proved to be the drugs that changed the face of HIV-1 treatment and the pandemic in general.

For the first time the people ‘on the front line’ were at the table influencing the decisions so I was shocked to learn through the New York Times in December 2012 that Spencer himself had died after he stopped taking his life-saving medications and had succumbed to pneumonia brought about by HIV. Why would the person who fought for these drugs cause his own death?

Another reported case has been that of Dr Gabe Torres, the first director of the St Vincent’s Hospital AIDS programme in New York’s West Village, one of the death centres in the city which at the peak of the epidemic was losing a third of its patients each day. After years of fighting, the introduction of HIV drugs meant he had less to fight. In order to (in his own words) “celebrate living,” Gabe turned to recreational drugs, became infected with HIV and lost his license to practice medicine. We need to understand why these guys acted like this. We owe it to them and others alike to figure it out in order to intervene.

These may be isolated incidents, but what these individuals have been through cannot be ignored. In the same way we need to look for future situations where HIV/AIDS can strike. In recent years numerous HIV vaccine trials have been conducted, but some were prematurely halted because the vaccine was associated with a higher risk of infection when compared to the placebo.

The mechanism resulting in higher transmissions is not known, but given that HIV infects immune cells, it is likely due to the immune activation that the vaccine stimulated. This is exactly what a vaccine is meant to do, but rather than induce a protective response, the activated immune cells have been rendered more prone to infection with HIV. Not all HIV vaccines tested to date have demonstrated this enhancing effect, but the individuals from such trials need to be carefully monitored.

Psychological implications

How will someone feel who has volunteered for a study and is infected with HIV? Although infection can never be linked specifically to the vaccine, human nature is such that they may blame themselves for becoming involved with such a trial. We have recently published that neutralising antibodies against HIV are a magnitude higher in mothers who transmit the virus to their infants ‘in utero’ than those who do not. These are the same antibody responses that we all wish to see induced in HIV-1 vaccine recipients. This might mean that a vaccinated mother is at higher risk of transmitting the virus to her unborn child than if she was not vaccinated. This could have immense psychological implications.

Obviously vaccine trials need to go ahead and the science be pursued, but we need to consider the situations in which individuals can become unwittingly affected, HIV positive or otherwise, to be prepared to act and find explanations and solutions for the many complicated aspects of this disease. “